Recent animal studies have suggested a possible link between cellular prostaglandins (PGs) and the reactivation of latent herpes simplex virus (HSV). However, no study to date has examined the direct action of PGs on latent HSV.
The specific aim of this proposal will be to investigate the effects of PGs, cyclooxygenase inhibitors, and a lipoxygenase inhibitor on the in vitro and in vivo reactivations of latent HSV in the sensory ganglia of laboratory animals. We will inoculate the orofacial area of mice with HSV to establish a latent infection in the trigeminal ganglia. During latent period (4-8 weeks after viral inoculation), the ganglia will be excised and cultured in the presence of PGE2, PGF2, PGD2, specific cyclooxygenase inhibitors, e.g. indomethacin, flurbiprofen or ibuprofen, or a lipoxygenase inhibitor, norhydroguaiaretic acid (NDGA). The effect of PGs and enzyme inhibitors on the reactivation of latent HSV in vitro will be monitored by quantitating the amount of reactivated virus in ganglia. In order to study the action of PGs synthesis inhibitors and NDGA on the reactivation of latent HSV in vivo, rabbit corneas will be inoculated with HSV and latent viral infection will be established in the trigeminal ganglia. Following the establishment of latency, the latent virus will be manipulated to be reactivated by iontophoresis of epinephrine into the rabbit cornea. The effect of systemic PGs synthesis inhibitors and NDGA on the reactivation of latent virus will be studied by monitoring the viral shedding in tears and the determination of virus in ganglia. Through the above study we expect to obtain significant information on factors affecting HSV latency and reactivation.
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